Sunday, 4 November 2012

Talk : Crystallography

NCB was chuffed to be able to attend a recent Café Scientifique talk entitled “Crystal Gazing and X-Ray Phasing - molecular insights into blood clotting” and was presented by Prof Jonas Emsley (Professor of Macromolecular Crystallography, Faculty of Science, University of Nottingham)

Prof Emsley began by describing some of the many types of crystals, including Diamond and, surprisingly, Chlolesterol, which forms potentially dangerous crystals within the human body.

White crystals of Chlolesterol

Crysallography, can be broken down into two main areas - the study of small molecules and the study of large molecules. The work Prof Emsley is involved in concerns large molecules, known as “macromolecules” such as collagen, the most common protein in the body.

Collagen Triple Helix

Fibers of Collagen

Crystallography involves determination of the structure of a molecule by various means. One of the primary tools is to use X-Rays, which are diffracted by the crystal structure to form a pattern of dots. Examination of the location and pattern of the dots allows researchers to determine the structure of the molecule under examination.

Typical X-Ray Diffraction Pattern

The first challenge is to find a way of encouraging a sample of the macromolecule to actually form a crystal, usually by combining the macromolecules with the right amount (up to 70%) of water to form a water loaded crystal. A typical crystal is around 0.1mm in size. Anything around 1mm in size would be dubbed by Prof Emsley’s team as a “King Kong” crystal.

It can then be subjected to diffraction in a diffractometer, where X-rays are generated in a synchrotron and fired at the crystal, with the diffracted beam being imaged on the other side of the crystal, often on a CCD device. The sample may be frozen so to combat the effects of heating from the X-rays.

An X-Ray Diffractometer used by Prof Emsley's team

Typical Lattice in a macromolecule crystal, with gaps being filled with water

Advanced techniques may be required to determine the structure of particularly complex proteins. One example is Serum Amyloid P, which plays a part in the formation of harmful Amyloid deposits around the body of people who are susceptible to their formation

Serum Ayloid P

Prof Emsley then looked at a number of aspects of the blood clotting process, starting with the point that blood needs the ability of clot to allow it to form a solid lumps where arteries, skin etc are broken. One participant in this process is the protein Thrombin which converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.

Thrombocin

Incidentally, some snake venoms contain powerful coagulants. Somewhat ironically these venoms cause so much of the body’s clotting factors to be used up that the victim can suffer from bleeding elsewhere in the body. Check out this rather sobering video clip to see what the snake venom can do (NSB notes that the video is edited and we only have the narrators word that the blood clots “in seconds”. Clip also has a foreign voiceover)

Prof Emsley pointed out that there was a need for novel anticoagulants that had a more consistent effect than Aspirin in reducing the risk to blood clots forming in patients suffering from coronary heart disease. One example of such a drug was Plavix

As an aside, the Prof mentioned recommended a book entitled “Max Perutz and the Secret of Life” by Georgina Ferry (see review here). The book describes the work of eccentric molecular biologist Max Perutz who won a Nobel Prize in 1962 for determining the structure of haemoglobin. As you can see from the image below, this was no mean feat.

Haemoglobin

During the question and answer session after the talk, Prof Emsley described a novel type of antibiotic that worked on the basis of disrupting the “quorum sensing” ability of bacteria. Bacteria form colonies within the human bodies and it is when they form these large communities, in which the bacteria communicate with each other, that they can be dangerous. These novel anti-biotics aim to disrupt this communication process (Bang Goes The Theory clip here).

And lastly, the Prof was asked whether his work with Crystallography ever spilled over into his everyday life, to which he replied that, to be fair, he was rather sensitive to the nature of symmetry patterns in wallpaper, noting that wallpaper can show 4-fold or 6-fold symmetry but never 5-fold or 7-fold symmetry.

NSB wonders whether this might form the basis for a cheeky question to staff at B&Q when purchasing wall coverings….

Rating on the NSB Science Accessability Criteria.
Where NSB has actually attended the talk (as opposed to getting a set of slides afterwards), NSB is able to rate the talk according to the "NSB Science Accessability Criteria" questions, and has done so on this occasion, with results shown below:

1) Does the organisation have a central list of all events? Yes
2) It is clear, before the talk starts , whether the slides will be available on the Internet or by email? No
3) Are links provided for people to find out more information? No
4) Are papers that are referred easily accessible, in full, to the public? Could not write down refernces in time, so not checked